Peptidases cytosolic

The coupling of solute transport in the GI lumen with solute lumenal metabolism (homogeneous reaction) and membrane metabolism (heterogeneous reaction) has been discussed by Sinko et al. [54] and is more generally treated in Cussler s text [55], At the cellular level, solute metabolism can occur at the mucosal membrane, in the enterocyte cytosol, and in the endoplasmic reticulum (or microsomal compartment). For peptide drugs, the extent of hydrolysis by lumenal and membrane-bound peptidases reduces drug availability for intestinal absorption [56], Preferential hydrolysis (metabolic specificity) has been targeted for reconversion... 

The intestinal mucosal peptidases are distributed in the brush border and cytosol of the absorptive cell. There are, however, distinct differences between the brush border and cytosolic peptidases [75], The tetrapeptidase activity is associated exclusively with the brush border enzyme. Furthermore, brush border peptidases exhibit more activity against tripeptides than dipeptides, whereas the cytosolic enzymes show greater activity against dipeptides. Studies have demonstrated that more than 50% of dipeptidase activity was detected in the cytosol [76] and just 10% in the brush border membrane [77]. The brush border enzymes include... 

Several different types of proteases hydrolyze intact storage proteins first into large fragments and then into smaller peptides and amino acids within the protein body. The peptides are transported to the cytosol where other enzymes, e. g. amino-peptidases, carboxypeptidases, dipeptidases and tripeptidases, cleave them and eventually form a pool of free amino acids [11]. 

High-molecular-weight complex peptidases composed of a series of low-molecular-weight subunits are found in the cytosol [27], These enzymes were... 

Calpains are enzymes that consist of a proteolytic subunit and a calcium binding subunit. In the cytosol, these enzymes are inactive due to binding of the inhibitory protein, calpastatin. Attachment to the cell membrane removes this inhibition and activation occurs at low concentrations of Csi ions. The enzymes hydrolyse proteins as far as peptides complete hydrolysis requires peptidases, which are also present in the cytosol. 

This enzyme [EC 3.4.19.5], now known as /3-aspartyl-peptidase, is a mammahan cytosolic protein that catalyzes the hydrolysis of a /3-hnked aspartyl residue from the N-terminus of a polypeptide. Other isopeptide linkages (e.g., a y-glutamyl hnkage) are not hydrolyzed by this enzyme. 

There are many dipeptidases [EC 3.4.13.x]. Cytosol nonspecific dipeptidase [EC 3.4.13.18] (also referred to as peptidase A, glycylglycine dipeptidase, glycylleucine dipeptidase, and A -)3-alanylarginine dipeptidase) catalyzes the hydrolysis of dipeptides. Membrane dipeptidase [EC 3.1.13.19] (also known as microsomal dipeptidase, renal dipeptidase, and dehydropeptidase I) is a zinc-dependent enzyme (a member of the peptidase family M19) that also catalyzes the hydrolysis of dipeptides. 

This zinc-dependent enzyme [EC 3.4.11.1], also referred to as cytosol aminopeptidase, leucyl aminopeptidase, and peptidase S, catalyzes the hydrolysis of a terminal peptide bond such that there is a release of an N-terminal amino acid, Xaa-Xbb-, in which Xaa is preferably a leucyl residue, but may be other aminoacyl residues including prolyl (although not arginyl or lysyl). Xbb may be prolyl. In addition, amino acid amides and methyl esters are also readily hydrolyzed, but the rates with arylamides are exceedingly slow. The enzyme is activated by heavy metal ions. 

This manganese-dependent enzyme [EC 3.4.13.9] (also known as Xaa—Pro dipeptidase, X—Pro dipeptidase, imidodipeptidase, prolidase, peptidase D, and y-pepti-dase) catalyzes the hydrolysis of Xaa—Pro dipeptides (except for prolylproline). The dipeptidase also acts on aminoacylhydroxyproline derivatives. This cytosolic enzyme, a member of the peptidase family M24A, is found in most animal tissues. 

This manganese-dependent enzyme [EC 3.4.11.5] catalyzes the release of an N-terminal prolyl residue from a peptide. The mammalian enzyme, which is not specific for prolyl bonds, is possibly identical with cytosol amino-peptidase [EC 3.4.11.1]. 

Probably the most important protective mechanisms involve the tripeptide GSH (chap. 4, Fig. 59). This compound is found in most cells, and in liver cells, it occurs at a relatively high concentration, about 5 mM or more. There are three pools of GSH cytosolic, mitochondrial, and nuclear. GSH structure is unusual for a peptide in the glutamyl, and cysteine residues are not coupled via a peptide bond, hence the molecule is resistance to peptidase attack. It has a nucleophilic thiol group, and it can detoxify substances in one of three ways ... 

Botulinum toxin is a mixture of six large molecules, each of which consist of two components, a heavy (lOOkDa) and light (50kDa) polypeptide chain. The heavy chain binds to the walls of nerve cells, which then allows the whole toxin molecule to be transported into the cell inside a vesicle via receptor-mediated endocytosis. Once inside, the light chain translocates into the cytosol and acting as a peptidase, destroys a synaptosomal protein. 

Proteasomes rather than cytosolic carboxy-peptidases act to trim the C-terminal amino acids to conform the peptide to the proper size for MHC class-I presentation. Presentation from N-extended precursors is inhibited by acetylation of the terminal a-amino group at the N-terminus [354], which prevents the peptide to be cleaved by aminopeptidases e.g. leucine aminopeptidase) but not by proteasomes or endopeptidases. The TAP system transports peptides to the ER including both mature epitopes and longer precursors. It seems then that the peptides to be presented by MHC class-I can arise from N-extended precursors both in the cytosol and in the endoplasmic reticulum (ER). This assertion has been experimentally confirmed [355,356]. 

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